Cerebrospinal fluid exposure of JNJ-54861911 [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]

The number of volunteers who experience adverse events as a measure of safety and tolerability of JNJ-54861911 after multiple-dose administration in the anticipated target dose range [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]

Compare the relationship of amyloid beta 1-40 levels in plasma and cerebrospinal fluid after treatment at the intended target dose range [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]

From Day 1 to Day 28 inclusive, patients will self-administer once daily study drug (JNJ-54861911 or placebo) with a glass of non-carbonated water (approximately 200 mL).

Drug: JNJ-54861911 10 mg

JNJ-54861911 10 mg will be administered as two 5 mg oral tablets once daily.

Experimental: JNJ-54861911 50 mg

Drug: JNJ-54861911 50 mg

JNJ-54861911 50 mg will be administered as two 25 mg oral tablets once daily.

Placebo Comparator: Placebo

Patients will receive matching placebo.

Drug: Placebo

Matching placebo will be administered as 2 oral tablets once daily.

Detailed Description:

This will be a multicenter, double-blind (neither investigator nor patient knows which treatment the patient receives), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), randomized (patients are assigned different treatments based on chance), multiple-dose, proof-of-mechanism (POM) study in pAD. Approximately 24 outpatients (n=8/treatment group) diagnosed with pAD, according to the inclusion and exclusion criteria, will participate in this 4-week treatment study. For all enrolled patients, this study will consist of an 8-week eligibility screening period, a 4-week double-blind treatment period, and a follow-up examination (7-14 days after the last dose). Patients will be assigned randomly to 1 of 3 treatment groups: placebo, JNJ-54861911 10 mg once daily, or JNJ-54861911 50 mg once daily. Safety assessments will be performed throughout the study. The maximal study duration for a patient will be 14 weeks.

Eligibility

Ages Eligible for Study:

50 Years to 90 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients must have had sufficient education or work experience to exclude mental retardation

Patients must have an abnormal cognitive performance consistent with mild cognitive impairment based on the computerized neuropsychological test battery (CANTAB Elect) that can effectively screen patients and identify cognitive deficits consistent with mild cognitive impairment

Patients must have evidence of amyloid deposition by means of either 1) low cerebrospinal fluid amyloid beta 1-42 (CSF amyloid beta 1-42) levels and elevated CSF p-Tau and/or total tau levels at screening (cut off values for CSF amyloid beta 1-42 and CSF p-tau and/or total tau will be based on the values established by the Clinical Neurochemistry Lab, Sahlgrenska University Hospital, Mölndal, Sweden and specified in a separate lab manual) or 2) a positive 18F-flutematol amyloid positron emission tomography (PET) amyloid scan at screening (optional depending on the site's PET capability) or both

Patients must have a body mass index (BMI=weight/height²) between 18 and 35 kg/m2, inclusive, at screening

Women must be postmenopausal, permanently sterilized or otherwise be incapable of pregnancy

Must adhere to required contraception during and for 3 months after study

Patients must be otherwise healthy for their age group or medically stable with or without medication

Patients must be able to be compliant with self-administration of medication

Patients must be able to swallow drug as a whole

Exclusion Criteria:

Patient has evidence of brain disease, other than Alzheimer's Disease (AD), or any other abnormality (e.g. folic acid/Vitamin B12 deficiency) that could explain the cognitive deficit (including, but not limited to vascular encephalopathy or strokes, as imaged by cerebral MRI and Major Depression, as defined by DSM-IV criteria)

Patient has been diagnosed with dementia due to AD, due to other diseases, or with AD and contribution of other disorders (mixed dementia)

Patient has evidence of familial autosomal dominant AD

Patient has a history of substance or alcohol abuse

Relevant history of lower back pain or scoliosis and/or major (lumbar) back surgery

Patient is allergic to local anesthetics and/or iodine or chlorhexidine

Patient has taken aspirin (even low dose) within 5 days prior to lumbar puncture (screening or Day 1)

Patient has taken Low Molecular Weight Heparin (LMWH) within 12 hours prior to lumbar puncture (screening or Day 1)

Patient has taken any anticoagulant treatment (e.g. warfarin; besides LMWH described above) within 1 week prior to lumbar puncture (screening or Day 1)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01978548